J . O r g . C h e m . 1994,59, 6887-6889
6887
Asymmetric Carboalkoxyalkylidenation with a Chiral Homer-Wadsworth-Emmons Reagent Scott E. Denmark* and Isaac Rivera Roger A d a m s Laboratory, Department of Chemistry, University of Illinois, Urbana, Illinois 61801 Received July 19, 1994@
Summary: The asymmetric carboalkoxyalkylidenation of 4-substituted cyclohexanones was effected by the use of chirally modified Horner-Wadsworth-Emmons (HWE) reagents in good yields ( 7 8 4 2 % ) as well as high levels of enantioselectivity (78-86% ee). The Horner-Wadsworth-Emmons (€!NE) reaction between phosphorus-stabilized carbanions and aldehydes or ketones is an important and practical method for the construction of carbon-carbon double bonds (Scheme l).l The reaction generally occurs at lower temperatures and encompasses a greater spectrum of carbonyl compounds than the conventional Wittig reaction of phosphorus ylides.2 Many attempts to develop an asymmetric version of the €!NE reaction have been reported over the past three decades. Since the pioneering work by Bestmann, which employed chiral phosphoranes for the synthesis of optically active allenes and ~ycloalkylidenes,~*-~ other phosphorus-based reagents have been developed. Chirally modified phosphinothioic amides,4aphosphonamides,4b-d phosphine and oxazapho~phorinanes~g have been used for the selective preparation of alkyl- or arylsubstituted chiral alkylidenes. In addition, the synthesis of functionalized, optically active olefins has been addressed and acyl- and carbalkoxyalkylidenes have been prepared as well from phosphorus reagent^.^ For example, chiral phosp h i n a t e ~ , p~ h” o~ s p h o n a t e ~ , oxathiapho~phorinanes,~’ ~~-~ @Abstractpublished in Advance ACS Abstracts, October 15, 1994. (1) (a) Homer, L.; H o f i a n n , H.; Wippel, H. G. Chem. Ber. 1968, 91,61. (b) Wadsworth, W. S.; Emmons, W. D. J. Am. Chem, SOC.1961, 83,1733. (c)Wadsworth, W. S., Jr. Org. React. 1977,25,73.(d)Walker, B. J. In Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic Press: New York, 1979; Chapter 3. (2) (a) Gosney, I. Rowley, A. G. In Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic Press: New York, 1979; Chapter 2. (b) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89,863. (c) Kelly, S. E. In Comprehensive Organic Synthesis, Additions to C-XnBonds, Part 1; Schreiber, S. L., Ed.; Pergamon Press: Oxford, 1991; Vol 1;Chapter 3.1. (3) (a) Bestmann, H. J.; Tomoskazi, T. Tetrahedron Lett. 1964,20, 1293. (b) Bestmann, H. J.; Tomoskozi, T. Tetrahedron 1968,24,3299. (c) Bestmann, H. J.; Lienert, J. Angew. Chem., Znt. Ed. Engl. 1969,8, 763. (d) Bestmann, H. J.; Heid, E.; Ryschka, W.; Lienert, J. Liebigs Ann. Chem. 1974,1684. (4) (a) Johnson, C. R.; Elliot, R. C.; Meanwell, N. A. Tetrahedron Lett. 1982, 23, 5005. (b) Hanessian, S.; Delorme, D.; Beaudoin, S.; Leblanc, Y. J. Am. Chem. Soc. 1984, 106, 5754. (c) Hanessian, S.; Beaudoin, S. Tetrahedron Lett. 1992, 33, 7655. (d) Hanessian, S.; Beaudoin, S. Tetrahedron Lett. 1992, 33, 7659. (e) Polniazek, R. P.; Foster, A. L. J. Og. Chem. 1991,56,3137.(0 Warren, S.; Harmat, N. J. S. Tetrahedron Lett. 1990,31, 2743. (g) Denmark, S. E.; Chen, C.T. J. Am. Chem. Soc. 1992,114, 10674. (5) (a)Musierowicz, S.; Wr6blewski, A. E.; Krawczyk, K. Tetrahedron Lett. 1976, 437. (b) Musierowicz, S.; Wrbblewski, A. E. Tetrahedron 1980, 36, 1375. (c) Gais, H.J.; Schmiedl, G.; Ball, W. A.; Bund, J.; Hellmann, G.; Erdelmeir, I. Tetrahedron Lett. 1988, 29, 1773. (d) Rewinkel, H. Skupsch, J.;Vorbriiggen, H. Tetrahedron Lett. lSSS,29, 1775. (e) Narasaka, K; Hidai, E; Hayashi, Y.; Gras, J.-L. J.Chem. SOC., Chem. Commun. 1993,102. (0 Rein, T.; Kann, N. J.Org. Chem. 1993, 58,3802. (g) Fuji, IC;Tanaka, K.; Ohta, Y.; Taga, T. Tetrahedron Lett. 1993,34,4071.(h) Toda, F.; Akai, H. J.O g .Chem. 1990,55, 3446. (i) Koizumi, T.; Takahashi, T.; Matsui, M.; Maeno, N. Heterocycles 1990, 30, 353. (j) Trost, B. M.; Curran, D. P. J.Am. Chem. SOC.1980,102, 5699. (k) Trost, B. M.; Curran, D. P. Tetrahedron Lett. 1981,22,4929.
0022-326319411959-6887$04.50/0
Scheme 1
?f ’R-p-hZ
1. base ___L
R*
0 RAR,
X = 0,S
Z = H, Alkyl, COR, CN
)
2.
R~
1. base
and pho~phoranes~j,~ have been employed with variable success. The highest selectivity obtained with 4-substituted cyclohexanones is 46% de of the corresponding esters using a menthol-derived p h ~ s p h o n a t e .In ~ ~addition, other non-phosphorus-based methods have been reported.6 In continuation of our examination and development of chiral, phosphorus carbanionic reagents,4gs7we have devised a general procedure for the synthesis of (carboxyalky1idene)cycloalkanes from the corresponding ketones. To accomplish this transformation we have investigated the use oxazaphospholidine 2-oxides (6 and 71, which employ readily available, camphor-derived amino alcohol auxiliaries for the asymmetric modification of phosphorus (Scheme 2). The synthesis of the amino alcohols 3 and 5 began with camphorquinones (11, which was condensed with different primary amines to produce the corresponding keto imines 2 in good yield^.^ Amino alcohols 3 were obtained by direct hydride reduction of the keto imines with either NaB& or Ca(BH&.’O In the case of the endo isomer, 5, a stepwise sequence of reductions was employed. Selective reduction of the imine double bond using either Zn/ KOH or hydrogen over Raney nickel afforded the a-amino ketones 4, which upon reduction with Ca(BH4)2 produced the endo amino alcohols 5.11 The exo phosphorus reagents (cis-and t r ~ n s - 6were ) ~ ~ synthesized by treatment (6) (a) Walborsky, H. M.; Duraisamy, M. J. Am. Chem. SOC.1983, 105, 3252. (b) Solladie, G.; Zimmermann, R.; Bartsch, R.; Synthesis 1986,662. (c) Duhamel, L.; Ravard, A.; Plaquevent, J X . ; Davoust, D. Tetrahedron Lett. 1987,28,5517. (d) Gaia, H.-J.; Erdelmeir, I.; Lindner, H. J. Angew. Chem., Znt. Ed. Engl. 1986, 25, 935. (e) Gais, H.J.; Erdelmeir, I. J. Am. Chem. Soc. 1989,111,1125. (0 Gaia, H.J.; Biilow, G. Tetrahedron Lett. 1992, 33, 465. (g) Sharpless, K B.; Van Nieuwenhze, M. S. J . Am. Chem. SOC.1993, 115, 7864. (h) Uemura, S.; Komatsu, N.; Matsunaga, S.; Sugita, T. J.Am. Chem. SOC.1993,115, 5847. (i) Legros, J.-Y.; Fiaud, J.-C. Tetrahedron 1994, 50, 466. (7) (a) Denmark, S. E.; Marlin, J. E. J. Org. Chem. 1991,56, 1003. (b) Denmark, S. E.; Stadler, H.; Dorow, R. L.; Kim, J.-H. J. Org. Chem. 1991, 56, 5063. (c) Denmark, S. E.; Chatani, N.; Pansare, S. V. Tetrahedron 1992,48,2191. (d) Denmark, S. E.; Amburgey, J. J. Am. Chem. SOC.1993, 115, 10386. (e) Denmark, S. E.; Chen, C.-T. J. Org. Chem. 1994,59, 2922. (8) (a)Bredt, J.;Holz, W. J.Prakt. Chem. 1917,95,135.(b) Arigoni, D.; Marquet, A.; Dvolaitzky, M. Bull. Chim. SOC. Fr. 1966, 9, 2956. (9) Forster, M. 0.;Thornley, T. J. Chem. SOC.1909, 95, 942. (10) (a)Saigo, K.; Yamamoto, M.; Morimura, K.; Nohira, H. Chem. Lett. 1979, 545. (b) Helmchen, G.; Selin, A,; Dorsch, D.; Taufer, I. Tetrahedron Lett. 1983,24, 3213.
0 1994 American Chemical Society
Communications
6888 J . Org. Chem., Vol. 59, No. 23, 1994
Table 1. Olefination of 4-tert-Butylcyclohexanonewith cis- and t r a n s - 6 6 I base
t - B u 0 0 THFIO'C
entw
1 2 3 4 5 6 7 8 9
lod 11 12 13'
R
compd
i-C4H9 trans-6a trans-6b i-C3H7 (CH3)3CCH2 trans-6d i-C4H9 cis-6a cis-6a i-C4H9 i-C3H7 cis-6b i-C3H7 &-6b &-6b i-C3H7 (CH3)3CCH2 cis-6d t-C4H9 cis-de &-6f CsH5 3,5-(CF&C& &-6h 3,5-(CF3)2CsH3&-6h
-
rBu*CO&H3 Ea
base KHMDS KHMDS KHMDS KHMDS
NaHMDS KHMDS
KHMDS' LDA
KHMDS KHMDS
KHMDS KHMDS KHMDS
time, yield," ee,* % h % (confgn) 1 1.5
3 1 1 1 2.5 3.5 2 24 2 9 48
60 70 92 47 58 68 16 49 59
